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ΔFosB accumulates in a GABAergic cell population in the posterior tail of the ventral tegmental area after psychostimulant treatment

Perrotti, Linda I., Bolaños, Carlos A., Choi, Kwang‐Ho, Russo, Scott J., Edwards, Scott, Ulery, Paula G., Wallace, Deanna L., Self, David W., Nestler, Eric J., Barrot, Michel·2005·European Journal of Neuroscience

DOI 10.1111/j.1460-9568.2005.04110.x

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Abstract

The transcription factor deltaFosB is induced in the nucleus accumbens and dorsal striatum by chronic exposure to several drugs of abuse, and increasing evidence supports the possibility that this induction is involved in the addiction process. However, to date there has been no report of deltaFosB induction by drugs of abuse in the ventral tegmental area (VTA), which is also a critical brain reward region. In the present study, we used immunohistochemistry to demonstrate that chronic forced administration of cocaine induces deltaFosB in the rat VTA. This induction occurs selectively in a gamma-aminobutyric acid (GABA) cell population within the posterior tail of the VTA. A similar effect is seen after chronic cocaine self-administration. Induction of deltaFosB in the VTA occurs after psychostimulant treatment only: it is seen with both chronic cocaine and amphetamine, but not with chronic opiates or stress. The expression of deltaFosB appears to be mediated by dopamine systems, as repeated administration of a dopamine uptake inhibitor induced deltaFosB in the VTA, while administration of serotonin or norepinephrine uptake inhibitors failed to produce this effect. Time course analysis showed that, following 14 days of cocaine administration, deltaFosB persists in the VTA for almost 2 weeks after cocaine withdrawal. This accumulation and persistence may account for some of the long-lasting changes in the brain associated with chronic drug use. These results provide the first evidence of deltaFosB induction in a discrete population of GABA cells in the VTA, which may regulate the functioning of the brain's reward mechanisms.

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Authors: Perrotti, L. I., Bolaños, C. A., Choi, K., Russo, S. J., Edwards, S., Ulery, P. G., Wallace, D. L., Self, D. W., Nestler, E. J., & Barrot, M.
Affiliations: The University of Texas Southwestern Medical Center (US)
Florida State University (US)
Centre National de la Recherche Scientifique (FR)
ORCID: Perrotti, Linda I.
Choi, Kwang‐Ho
Russo, Scott J.
Edwards, Scott
Wallace, Deanna L.
Self, David W.
Nestler, Eric J.
Barrot, Michel
Venue: European Journal of Neuroscience
Publisher: Wiley
Published: 2005-05
Volume: 21
Issue: 10
Pages: 2817-2824
ISSN: 0953-816X (ISSN-L)
1460-9568
DOI: 10.1111/j.1460-9568.2005.04110.x
OpenAlex: W1967616722
Cited by: 178
References: 61
Citations by year: 2025: 3 · 2024: 10 · 2023: 1 · 2022: 4 · 2021: 5 · 2020: 12 · 2019: 9 · 2018: 5 · 2017: 5 · 2016: 17 · 2015: 9 · 2014: 14 · 2013: 9 · 2012: 14
FWCI: 3.14
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 26 d)
Locations: European Journal of Neuroscience (publishedVersion)
PubMed (publishedVersion)
HAL (submittedVersion)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
Keywords: ΔFosB, ventral tegmental area, GABAergic neurons, cocaine, amphetamine, psychostimulants, drug addiction, dopamine, brain reward, cocaine self-administration, cocaine withdrawal, chronic drug exposure, transcription factor induction
MeSH terms: Animals, Cocaine, gamma-Aminobutyric Acid, Kinetics, Male, Morphine, Self Administration, Transcription Factors, Proto-Oncogene Proteins c-fos, Rats, Sprague-Dawley, Ventral Tegmental Area, Cocaine-Related Disorders, Rats

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ΔFosB accumulates in a GABAergic cell population in the posterior tail of the ventral tegmental area after psychostimulant treatment

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